Background: Coronary computed tomographic angiography (CCTA) image quality is dependent on heart rate (HR). Beta blockers are commonly administered before CCTA to lower HR and minimize variability. However, contrast media may also impact upon HR and image quality. Since iso-osmolar contrast media induce less vasodilation, this may decrease a patient’s sensation of heat, minimizing patient discomfort and improving HR control and variability.

Objectives: The aim of the study was to compare the impact of contrast media selection in CCTA upon HR and image quality.

Patients and Methods: A total of 173 patients undergoing CCTA between February and April 2011 were allocated to different contrast media (Iodixanol, Iohexol, and Iopamidol) in 2-week blocks. The groups were analyzed for differences in baseline characteristics, imaging parameters, image quality, HR, and HR variability. Patients were also surveyed for perception of heat.

Results: Baseline HR was similar across the patients assigned to Iohexol, Iopamidol, and Iodixanol (65.3 ± 9.7, 66.9 ± 10.9, and 65.3 ± 13.3, respectively; P = NS). Compared to Iohexol and Iopamidol, Iodixanol use was associated with lower HR at the time of image acquisition and immediately after CCTA (53.2 ± 8.0 bpm, 56.3 ± 7.8 bpm, and 56.8 ± 6.5 bpm; P = 0.069 and P = 0.032). A greater proportion of patients achieved HR ≤ 55 beats per minute (bpm) with Iodixanol (63%) than with Iohexol (42%; P = 0.025) and Iopamidol (39%; P = 0.011). As was expected, Iodixanol (2.34 ± 2.02) was associated with a lower perception of heat than Iohexol (6.13 ± 1.89; P < 0.001) and Iopamidol (5.22 ± 2.10; P < 0.001). Image quality was similar in all three groups.

Conclusions: Compared to Iohexol and Iopamidol, Iodixanol use was associated with a lower patient perception of heat and lower HR while maintaining similar contrast-to-noise and signal-to-noise ratios.

Coronary computed tomographic angiography (CCTA) is a useful noninvasive tool for the detection and exclusion of coronary artery disease (CAD). However, CCTA image quality is dependent on heart rate (HR) control, therefore requiring the use of beta-blockers to target HR ≤ 60 beats per minute (bpm) (1, 2). Beta blockers are not fully effective in all patients; therefore, patients who may barely meet HR control prior to CCTA may be more vulnerable to contrast-induced increases on HR (3, 4). HR may also be influenced by patient discomfort during contrast injection. Though many contrast agents share the same toxicities, some have been associated with less arterial vasodilation (5-7). A heat or warming sensation experienced during intravenous injection of contrast media is common and may cause patient discomfort and anxiety (8). This in turn could increase HR during image acquisition. The sensation of heat varies with differing contrast media, with iso-osmolar media (Iodixanol) producing less heat than low-osmolar media (Iohexol and Iopamidol) (5). Previous studies have documented HR changes with various contrast media during invasive coronary angiography and pulmonary CT angiography (9, 10). However, there are limited studies examining contrast-mediated HR variability and image quality with CCTA (11, 12).

The objective of this study was to compare the impact of contrast media selection in CCTA upon HR and image quality.

3.1. Study Design

As part of an institutional quality assurance evaluation, 197 patients who underwent CCTA over a 6-week period were screened. A total of 173 patients who were eligible to receive any contrast media were prospectively enrolled in the CT registry and voluntarily completed a heat sensation survey. Over the 6-week study period, the three contrast agents were randomly assigned to 2-week blocks. Both patients and nurses (who administered beta blockers) were blinded to contrast allocation. Patients consented to the cardiac CT registry, and retrospective analysis of CT registry data was approved by the local institutional review board.

4.1. Patient Demographics

A total of 173 patients (49% men, mean age = 58.2 ± 12.2 years, body mass index [BMI] = 30.2 ± 5.6 kg/m², and GFR = 94.2 ± 31.6 mL/min) underwent CCTA and were enrolled in the study (Table 1). Patients with atrial fibrillation or arrhythmia were excluded. Between the three groups, there were no statistically significant differences in age, sex, BMI, GFR, cardiac risk factors, baseline HR, baseline blood pressure, obstructive CAD, and history or prior percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).

Table 1. Baseline Patient Characteristics a,b,c

4.2. Beta-Blocker Administration

Chronic and pre-CT beta-blocker use was similar across all three groups (Tables 1 and 2). The dose required per patient receiving IV beta-blockers and the baseline and pre-CT HR were not significantly different between the three groups.

Table 2. Pre-Computed Tomography Protocol a,b

4.3. Computed Tomography Imaging Parameters

Although there were significant differences in CT imaging parameters identified between the three contrast media, there were no significant differences in CT imaging parameters between Iodixanol and the other two contrast media using the Tukey HSD post-hoc tests (Table 3).

Table 3. Computed Tomography Imaging Parameters a

4.4. Heart Rate

HR at baseline and after beta-blocker administration was similar in all 3 groups (Table 4). HR at the time of CCTA image acquisition was lower with Iodixanol (53.2 ± 8.0 bpm) than with Iohexol (56.3 ± 7.8 bpm; P = 0.069) or Iopamidol (56.8 ± 6.5 bpm; P = 0.032). Similarly, HR 30 seconds after image acquisition was significantly lower with Iodixanol (58.9 ± 7.1 bpm) than with either Iohexol (64.4 ± 7.8 bpm; P < 0.001) or Iopamidol (62.9 ± 7.2; P = 0.012).

The proportion of patients in each group that achieved an imaging HR ≤ 55 bpm was significantly greater with Iodixanol (63%) than with Iohexol (42%; P = 0.025) or Iopamidol (39%; P = 0.011). The difference in achieving HR ≤ 60 with Iodixanol (84%), Iohexol (75%), and Iopamidol (70%) was not significant. HR variability between the three contrast media was similar during image acquisition (Table 4).

Table 4. Heart Rate a,b

4.6. Image Quality

Attenuation of the aorta, signal-to-noise, and contrast-to-noise was similar between all contrast media (Table 5). However, noise in the aorta appeared to be lower with Iodixanol (35.6 ± 8.4 HU) when compared to Iopamidol (40.1 ± 10.3 HU; P = 0.039), but no statistically significant difference was observed between Iodixanol and Iohexol. There was no difference in non-evaluable coronary artery segments (P = 0.481) in the groups that received Iodixanol (4.8% [44/919 segments]), Iohexol (5.8% [57.976 segments]), and Iopamidol (8.2% [76.930 segments]). Similarly, no differences were observed in the three groups when patients with history of PCI or CABG were excluded from analysis. On a per-patient analysis (patients without revascularization), patients with ≥ 1 non-evaluable segment appeared to be fewer in Iodixanol group (17.0%; 8.47 patients) than in Iohexol (26.4%; 14.53 patients; P = 0.373) and Iopamidol (31.2%, 15.48 patients; P = 0.169) groups, but statistical significance was not achieved.

Table 5. Image Quality Measures a,b

Our study demonstrates that Iodixanol, compared to Iohexol and Iopamidol, is associated with lower HR during image acquisition while maintaining image quality with similar contrast-to-noise and signal-to-noise ratios. The lower HR observed with Iodixanol may be due to the decreased perception of heat associated with iso-osmolar contrast agents. Although the discomfort caused by contrast-mediated heat sensation seems harmless, it may impact upon CCTA image quality by increasing HR and thus the likelihood of cardiac motion. As was expected, due to differences in iodine flux between the agents, the perception of heat was much lower with the iso-osmolar contrast medium (Iodixanol) and had lower HR with more patients achieving the target HR ≤ 55 bpm. This is important because studies have found that lower HR improves image quality (13). This improvement in HR control occurred while maintaining image quality despite lower iodine content in Iodixanol. Due to the dependence of CCTA on low and steady HR, effective control of HR is needed. Currently, beta blockers are the preferred medication for lowering HR in CCTA patients (19). Pannu et al. (4) showed that oral beta blockers (Metoprolol) given before CT were effective in lowering HR in 79.4% of patients, but the other 20.6% of patients had no change or an increase in HR during CT. They concluded that beta blockers were ineffective in a proportion of patients. de Graaf et al. (3) found that 16% of patients had contraindications to beta blockers and 27% were unable to achieve target HR despite beta-blocker administration. Given that some patients requiring HR control for CCTA do not respond to beta-blocker administration, identification of other methods such as selection of contrast media that minimize HR variability may improve the diagnostic accuracy of CCTA in these patients. The safety profile of the contrast media is important when selecting the ideal agent for different study populations. Both Iodixanol and Iopamidol, as well as non-ionic agents, are commonly used in patients with renal insufficiency due to their lower risk of nephrotoxicity (20). However, the impact of contrast media selection may affect CCTA in other ways. Previous studies comparing Iodixanol to other contrast media have shown fewer cardiovascular and renal adverse effects, while maintaining diagnostic equivalency (5, 21, 22). Similarly, HR with Iodixanol is lower, but studies have focused on patients undergoing invasive coronary angiography or pulmonary embolism studies, which are less dependent on HR (9, 10, 23). HR is an important factor in CCTA image quality, and minimizing patient-dependent factors such as anxiety and discomfort is desirable. By reducing heat sensations, one may be able to minimize HR changes and patient motion, which are relevant to single-source CT scanners with limited temporal resolution. Therefore, selection of the ideal contrast agent may involve more than considering its safety profile and also include its effects on HR and patient comfort. Previous intra-arterial studies have examined HR variability with different contrast media (11, 12). Becker et al. (12) showed no difference in HR when Iomeprol-400 and Iodixanol-320 were used. Conversely, Svensson et al. (11) demonstrated that HR was lower with Iodixanol-320 and was associated with less arrhythmia and heat sensation. Our study differs by demonstrating that Iodixanol was associated with lower HR and heat sensation when compared to Iohexol and Iopamidol while maintaining similar image quality and signal-to-noise ratios.